A mouse model characterizes the roles of ZIP8 in systemic iron recycling and lung inflammation and infection

Author:

Zhang Vida12,Jenkitkasemwong Supak3,Liu Qingli3,Ganz Tomas1ORCID,Nemeth Elizabeta1ORCID,Knutson Mitchell D.3ORCID,Kim Airie1

Affiliation:

1. 1Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA

2. 2Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA

3. 3Food Science and Human Nutrition Department, University of Florida, Gainesville, FL

Abstract

Abstract ZIP8 (SLC39A8) is a transmembrane divalent metal ion importer that is most highly expressed in the lung and is inducible by inflammatory stimuli. In addition to zinc and manganese, ZIP8 can transport iron, but its specific roles in iron regulation during homeostatic and pathologic processes remain poorly understood. Using a novel global inducible ZIP8 knockout (KO) mouse, we analyzed the role of ZIP8 in steady-state iron homeostasis and during inflammation and infection. We observed an unexpected phenotype of elevated spleen iron levels and decreased serum iron in ZIP8 KO mice, suggesting that ZIP8 plays a role in iron recycling. We also showed that ZIP8 is expressed on lung distal airspace epithelial cells and transports iron from the airway into lung tissue. LPS-induced inflammation induced ZIP8 expression in the lung, but ZIP8 deletion had no detrimental effect on the severity of LPS-induced acute lung injury or on the outcomes of Klebsiella pneumoniae lung infection. Thus, ZIP8 plays a role in systemic iron homeostasis but does not modulate the severity of inflammatory lung injury or the host defense against a common bacterial cause of pneumonia.

Publisher

American Society of Hematology

Subject

Hematology

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